Exploring Strategies for Personalized Radiation Therapy Part IV: An Interaction-Picture Approach to Quantifying the Abscopal Effect

Abstract: We revisit the controversial "abscopal" effect in the context of Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR). By allowing long interval between fractions, PULSAR may enhance systemic immune activation and increase the likelihood of abscopal responses compared with conventional daily fractionation. To quantify treatment-induced effects, we introduce an interaction-picture transformation adapted from quantum mechanics, which separates intrinsic tumor growth from radiation and immune-mediated perturbations. In this preliminary study, we tested this method to two preclinical bilateral tumor models (4T1 and MC38). Our model provides a quantitative measure of the interaction strength between primary and secondary tumors at the individual level, capturing dynamics over time rather than relying solely on cohort averages. This approach frames the abscopal effect as a continuous, stochastic phenomenon rather than a binary response. The framework is flexible for future studies, particularly in concurrent radiation and immunotherapy with PULSAR, where different radiation doses and fractionation schedules can be compared, and immune checkpoint inhibitors (ICIs) can be incorporated to further enhance systemic anti-tumor immunity. The framework can also help us make cross-study comparison of abscopal effects and standardizes the reporting of abscopal magnitude beyond simple statistical significance.